gms | German Medical Science

56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
3èmes journées françaises de Neurochirurgie (SFNC)

Deutsche Gesellschaft für Neurochirurgie e. V.
Société Française de Neurochirurgie

07. bis 11.05.2005, Strasbourg

Mutational analysis of TOK-1 in pituitary adenomas

Mutationsanalyse von TOK-1 in Hypophysenadenomen

Meeting Abstract

  • corresponding author J. Kreutzer - Neurochirurgische Klinik, Universität Erlangen
  • V. Schmidt - Institut für Neuropathologie, Universität Erlangen
  • I. Blümcke - Institut für Neuropathologie, Universität Erlangen
  • R. Fahlbusch - Neurochirurgische Klinik, Universität Erlangen
  • R. Buslei - Institut für Neuropathologie, Universität Erlangen

Deutsche Gesellschaft für Neurochirurgie. Société Française de Neurochirurgie. 56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3èmes journées françaises de Neurochirurgie (SFNC). Strasbourg, 07.-11.05.2005. Düsseldorf, Köln: German Medical Science; 2005. DocP119

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2005/05dgnc0387.shtml

Published: May 4, 2005

© 2005 Kreutzer et al.
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Outline

Text

Objective

The gene encoding TOK-1 (BCCIP), a p21 binding protein and novel type of CDK2 modulator, is localized to chromosome 10q26. Recent studies suggest that a specific splice form, TOK-1a (BCCIPa), is an important cofactor for BRCA2 in tumor suppression. Due to frequent allelic deletions on chromosome 10q26 in pituitary tumors, a mutational analysis of TOK-1 in a large series of pituitary adenomas was performed.

Methods

Within the last decade, shock-frozen tumor samples from more than 500 patients with pituitary adenomas were collected. For RNA-/ and DNA extraction, the new Biorobot EZ1 automat (Qiagen) was used. In a series of 80 patients and 50 control samples, we studied the coding region of the TOK-1 gene using single-stranded-conformation-polymorphism (SSCP) analysis.

Results

We detected a point mutation in Exon 5 of the TOK-1 gene in one patient with an inactive pituitary adenoma causing a consecutive amino acid exchange from valin (GTG) to alanin (GCG). Furthermore, we detected a single nucleotide polymorphism from c>t just five bp in front of the Exon 7 starting site. This replacement was present in 2 tumors, but not in the control blood sample. Because Exon 7 is alternatively spliced resulting in two isoforms, TOK-1a and TOK-1b, further experiments will have to elucidate, whether the nucleotide exchange affects the splicing machinery.

Conclusions

This is the first study supporting a possible role of the CDK2/p21 modulator TOK-1 in the molecular pathogenesis of pituitary adenomas. Further analysis of the different splicing isoforms of TOK-1, their relevance with regard to the tumorigenesis and expression analysis utilizing a broader spectrum of tumor variants is mandatory to elucidate the role of TOK-1 in the development of neoplasms of the sellar region.